Afferent Integration in the NAcb MSP Cell (Wolf et al. 2005)

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Accession:112834
"We describe a computational model of the principal cell in the nucleus accumbens (NAcb), the medium spiny projection (MSP) neuron. The model neuron, constructed in NEURON, includes all of the known ionic currents in these cells and receives synaptic input from simulated spike trains via NMDA, AMPA, and GABAA receptors. ... results suggest that afferent information integration by the NAcb MSP cell may be compromised by pathology in which the NMDA current is altered or modulated, as has been proposed in both schizophrenia and addiction."
Reference:
1 . Wolf JA, Moyer JT, Lazarewicz MT, Contreras D, Benoit-Marand M, O'Donnell P, Finkel LH (2005) NMDA/AMPA ratio impacts state transitions and entrainment to oscillations in a computational model of the nucleus accumbens medium spiny projection neuron. J Neurosci 25:9080-95 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell;
Brain Region(s)/Organism:
Cell Type(s): Nucleus accumbens spiny projection neuron;
Channel(s): I Na,p; I Na,t; I L high threshold; I N; I T low threshold; I A; I h; I K,Ca; I Krp; I R; I Q;
Gap Junctions:
Receptor(s): GabaA; AMPA; NMDA;
Gene(s):
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Oscillations; Schizophrenia; Addiction;
Implementer(s): Wolf, John A. [johnwolf at warpmail.net]; Moyer, Jason [jtmoyer at seas.upenn.edu];
Search NeuronDB for information about:  GabaA; AMPA; NMDA; I Na,p; I Na,t; I L high threshold; I N; I T low threshold; I A; I h; I K,Ca; I Krp; I R; I Q;
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nacb_msp
tau_tables
readme.html
AMPA.mod
bkkca.mod *
cadyn.mod *
caL.mod *
caL13.mod *
caldyn.mod
can.mod *
caq.mod *
car.mod *
cat.mod *
GABA.mod *
kaf.mod *
kas.mod *
kir.mod *
krp.mod *
naf.mod *
nap.mod *
NMDA.mod
skkca.mod *
stim.mod *
_run_me.hoc
all_tau_vecs.hoc *
baseline_values.txt *
basic_procs.hoc
create_mspcells.hoc *
current_clamp.ses *
make_netstims.hoc
mosinit.hoc *
msp_template.hoc
nacb_main.hoc
netstims_template.hoc *
screenshot.jpg
screenshot2.jpg
stimxout_jns_sqwave.dat
synapse_templates.hoc
                            
//*************************************************************************
// create and set netstims using champawt(), chnmdawt(), chint()



objref ConnectAMPA_[1000]
objref ConnectNMDA_[1000]
objref ConnectGABA_[1000]		// GABA only in soma
objref ConnectFAKE_[1000]		// NetCon that allows me to deliver an event to netstims

objref vsrc_
objref vsrcg_
objref tsrc_
objref fakeit					// i need something to connect the fake NetCon to


// create ampa connections
proc champawt() {    nAMPA_WT = $1   
    for i = 0, cell_number-1 {
    
    	for j = 0, NGLU-1 {
           	k = j*cell_number + i
			ConnectAMPA_[k] = new NetCon( NS_NetStim[k].pp, MSP_Cell[i].synlist.object[j].pp, 0, 0, nAMPA_WT) 
        }
    }
 }


// create nmda connections
proc chnmdawt() {    nNMDA_WT = $1 
    for i = 0, cell_number-1 {

    	for j = 0, NGLU-1 {
            k = j*cell_number + i
	        ConnectNMDA_[k] = new NetCon( NS_NetStim[k].pp, MSP_Cell[i].synlist.object[j+NGLU].pp, 0, 0, nNMDA_WT) 
        }
    }
}


// create gaba connections
proc chgabawt() {    nGABA_WT = $1
    for i = 0, cell_number-1 {

        for j = 0, NGABA-1  {
            k = j*cell_number + i
            ConnectGABA_[k] = new NetCon( NS_NetStim[k+NGABA*cell_number].pp, MSP_Cell[i].synlist.object[j+2*NGLU].pp, 0, 0, nGABA_WT) 
        }
    }
}


// This procedure will use vector play to change the inputs for up and down states
proc chfreq() {		// downstate frequency, upstate frequency, time of cycle, gaba:ampa number inputs ratio
    nDS_FRQ = $1
    nUS_FRQ = $2
    nT_CYCLE = $3
    nGA_RATIO = $4

    ncyc = 7		// number of cycles, as in 1 ds, 1 us, 1 ds, 1 us, 1 ds = 5

    tsrc_ = new Vector( 20, 10e5)		// used for predicting the interval changes for jstims
    for i = 0, ncyc-2 {tsrc_.x[i] = (i+1)*nT_CYCLE}	// netstims do not change interval until new spike is registered - jstim fixes this
    tsrc_.play( "for i = 0, NSYN-1 {NS_NetStim[i].pp.change = $1}", nT_CYCLE-dt)

    vsrc_ = new Vector( 20, nDS_FRQ) 		// init to down state frequency
    vsrc_.x[1] = nUS_FRQ 				// higher frequency for up states
    vsrc_.x[3] = nUS_FRQ
    vsrc_.x[5] = nUS_FRQ
    vsrc_.x[7] = nUS_FRQ
    vsrc_.play(" for i = 0, NGLU-1 { NS_NetStim[i].pp.frequency = $1 }", nT_CYCLE-dt )

    vsrcg_ = new Vector( 20, nDS_FRQ*(NGLU/NGABA)*nGA_RATIO)	// inputs to gaba netstims
    vsrcg_.x[1] = nUS_FRQ * (NGLU/NGABA) * nGA_RATIO	
    vsrcg_.x[3] = nUS_FRQ * (NGLU/NGABA) * nGA_RATIO	
    vsrcg_.x[5] = nUS_FRQ * (NGLU/NGABA) * nGA_RATIO	
    vsrcg_.play(" for i = NGLU, NGLU+NGABA-1  { NS_NetStim[i].pp.frequency = $1 }", nT_CYCLE-dt )
}





proc make_netstims() {
	for i = 0, NGLU*cell_number-1 {		// cortical cells 
		cell_append(new NS_NetStim(), 0, 0, 0)
	}

	for i = NGLU*cell_number, (NGLU+NGABA)*cell_number-1 {	//makes NGABA interneurons
		cell_append(new NS_NetStim(), 0, 0, 0)
	}

	for i = 0, (NGLU+NGABA)*cell_number-1 {
		ConnectFAKE_[i] = new NetCon( fakeit, NS_NetStim[i].pp,1,0,1) 	// source, target, threshold, delay, weight
	}			// now, ConnectFAKE_ can be used to deliver an event to NetStim from hoc

	champawt(AMPA_WT)  
	chnmdawt(NMDA_WT)
	chgabawt(GABA_WT)

	gampa(G_AMPA)
	gnmda(G_NMDA)
	ggaba(G_GABA)
	
	chfreq(0,0,284,1)  // downstate frequency, upstate frequency, time of cycle, GABA:AMPA ratio
}

make_netstims()
setnetn(0)			// allows events to played into NetCons via ConnectFAKEs

print "cells loaded"




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